The way I see it, the central problem with the game is simple: It's the enemies themselves, not the layouts or anything like that. And defnitely not ALL of the enemies, no no no. It's a few very specific ones that can cause problems.
Particularly at higher levels; some foes scale BADLY, and can become literally impossible to kill without getting hit, no matter what you have and what you do.
Scorpions, for example. Almost all of the time, at higher difficulties, you CANNOT kill these without taking a hit. They simply fire waaaaaayyyyyyy too often. When the first fire wave is just about done, they're standing still, and about to fire the next wave. You cant pierce those waves, and many ranged attacks dont actually have enough range for you to be out of the flame radius while still being in range to hit them. The one, and only, thing that I've found that works against them is snake attacks.... but that's mostly for caverns. It's not so good at all on overland sequences.
The pigeons are not quite as nasty.... their attacks CAN be dodged.... but they fire so frequently that you just cant hit them most of the time. Unlike the scorpions though it's safe to get on a platform with them and pop them when they're coming around a corner.
These are pretty much the two most aggravating enemies in the game, and they appear VERY frequently. They're not nearly as bad on lower difficulties, but they're a nightmare on the high ones.
The Eels have basically the same attack as the scorpions, but they do not cling to walls; they're dangerous as heck, but you can get into positions to hit them without immediately getting blasted. Their attack works out for them; the scorpions, honestly, probably should have a different attack type.
They're even worse with certain mage classes. In my current game, there is no such thing as a good ranged attack that has actual speed to it's projectiles. I mostly got Drone shots, and V shots... definitely useful to me in many situations, but they simply dont work against these foes at all. Ammo spells can help against them, but like all crawlers they're just too frequent. You dont have enough ammo to really use that as a viable method of defeating them.
Aurochs are pretty bad too. Usually undamageable on high difficulties. With the right setup though you can simply leap over them; their attacks are very predictable, if chaotic, and they're slower than a brick in sludge.
Or something like the Teleporting Ice Jerk. The one that fires a shot, and teleports to wherever the shot stops. It's fast enough, and fires frequently enough, that you dont have time to aim at it once it's somewhat close to you, depending on what spells you have. Ammo spells at least are much more viable against this guy. Bursts or crosses can take him down.
There's a couple of others.... but all in all, MOST enemies can be dealt with, technically, without you getting hit, even on high difficulties. It's just a matter of figuring out HOW. As well as knowing what mage classes to use, and what perks to set. I generally change classes and perks almost every single time I enter an area, in order to suit the situation.
The one other really major problem I'm aware of though is the game's extreme tendancy to spawn enemies right in front of the entrance to an area. Either in the same slice, or the slice next to it; often meaning that those enemies get a free shot at you that you may not be able to dodge.
Also: Screw mosquitoes. Argh. They're not unfair whatsoever, they're just..... argh. So..... irritating..... just stand still, dammit! Stop throwing those damn orange things at me!